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Protein C Promotor Haplotypes Associated with Large-Artery Atherosclerosis Stroke in Iranian Population

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Abstract

Ischemic stroke (IS) is a complex disease regarding its risk factors; among those factors, genetics has an important role. Protein C (PC) is an important antithrombotic enzyme which its genetic variations disrupt the normal cascade of blood coagulation, resulting in thrombosis and increases the chance of stroke. Therefore, we aimed to investigate three single-nucleotide polymorphisms (SNPs) located in the core promoter of PC in order to find their role in this condition in the Iranian population. Blood samples from IS patients (n = 249) and healthy volunteers (n = 203) were collected. Biochemical analysis was performed. Genotyping was conducted on the extracted DNA from blood samples via the HRM technique. Bioinformatic investigations were used to assess how these SNPs may be involved in the IS. Smoking, hypertension, low-density lipoprotein cholesterol, and fasting blood glucose were significantly different between healthy and IS groups. rs1799809 and rs1799810 SNPs were significantly more frequent among IS patients. Also, among four identified haplotypes, CGT was found associated with IS (p = 0.001). It was also found that these SNPs may interfere with the binding of transcription factors to alter the expression of PC. Our data predict that SNPs at the core promoter of PC can affect the binding affinity of transcription factors which in turn reduces the expression of PC and increases the risk of IS.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors highly appreciate the contributions of the Ghaem Hospital (Mashad, Iran) and the Vasei Hospital (Sabzevar, Iran) staff during this study.

Funding

The current study was generously supported by Sabzevar University of Medical Sciences (394212163).

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Author notes

  1. Seyed Elyas Meshkani and Ali Fasihi equally contributed to this work.

Authors and Affiliations

  1. Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Seyed Elyas Meshkani & Shahin Ramazi

  2. Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Ali Fasihi

  3. Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Fatemeh Badakhshan & Mohmmadsaeid Zahedi

  4. Iranian Research center on Healthy Aging, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Maryam Goudarzian

Authors
  1. Seyed Elyas Meshkani
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  2. Ali Fasihi
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  3. Fatemeh Badakhshan
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  4. Mohmmadsaeid Zahedi
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  5. Maryam Goudarzian
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  6. Shahin Ramazi
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Contributions

AF and SR designed experiments; SEM performed experiments and wrote the manuscript; FB, MZ, and MG provided instruments, chemicals, and samples; AF and SR performed the analysis of data; MZ reviewed and revised the manuscript based on new bioinformatics results.

Corresponding author

Correspondence to Shahin Ramazi.

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Ethical Approval

Human participant’s experiments and procedures were approved by the Sabzevar University Health Research Ethics Committee (IR.MEDSAB.REC.1394.186). No animal experiments were conducted in the current paper.

Informed Consent

All participants were enrolled in the study with informed consent.

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The authors declare that they have no conflict of interest.

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Meshkani, S.E., Fasihi, A., Badakhshan, F. et al. Protein C Promotor Haplotypes Associated with Large-Artery Atherosclerosis Stroke in Iranian Population. J Mol Neurosci 71, 2134–2141 (2021). https://doi.org/10.1007/s12031-021-01819-5

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  • DOI: https://doi.org/10.1007/s12031-021-01819-5

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